chr12-112919388-G-A

Position:

chr12-112919388-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016816.4(OAS1):c.1039-1G>A variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,598,136 control chromosomes in the GnomAD database, including 340,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28580 hom., cov: 32)

Exomes 𝑓: 0.65 ( 311607 hom. )

Consequence

OAS1
NM_016816.4 splice_acceptor

Scores

Splicing: ADA: 0.0007956

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.729

Variant links:

Genes affected

OAS1 (HGNC:8086): (2'-5'-oligoadenylate synthetase 1) This interferon-induced gene encodes a protein that synthesizes 2',5'-oligoadenylates (2-5As). This protein plays a key role in innate cellular antiviral response, and has been implicated in other cellular processes like cell growth and apoptosis. Alternative splicing results in multiple transcript variants with different enzymatic activities. Polymorphisms in this gene have been associated with susceptibility to viral infection, including SARS-CoV-2, and diabetes mellitus, type 1. This gene is located in a cluster of related genes on chromosome 12. [provided by RefSeq, May 2022]

OAS1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.802932).

BP6

Variant 12-112919388-G-A is Benign according to our data. Variant chr12-112919388-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1156518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-112919388-G-A is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_016816.4 linkuse as main transcript	c.1039-1G>A		splice_acceptor_variant		ENST00000202917.10	NP_058132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10 linkuse as main transcript	c.1039-1G>A		splice_acceptor_variant		1	NM_016816.4	ENSP00000202917	P2	P00973-1
	ENST00000552784.1 linkuse as main transcript	n.354-10710C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91290

AN:

151964

Hom.:

28562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.704

Gnomad FIN

AF:

0.728

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.592

GnomAD3 exomes

AF:

0.672

AC:

166967

AN:

248584

Hom.:

57604

AF XY:

0.672

AC XY:

90151

AN XY:

134228

show subpopulations

Gnomad AFR exome

AF:

0.417

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.787

Gnomad SAS exome

AF:

0.690

Gnomad FIN exome

AF:

0.738

Gnomad NFE exome

AF:

0.655

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.651

AC:

941833

AN:

1446056

Hom.:

311607

Cov.:

AF XY:

0.652

AC XY:

469297

AN XY:

719562

show subpopulations

Gnomad4 AFR exome

AF:

0.401

Gnomad4 AMR exome

AF:

0.783

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.690

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.648

Gnomad4 OTH exome

AF:

0.622

GnomAD4 genome

AF:

0.601

AC:

91352

AN:

152080

Hom.:

28580

Cov.:

AF XY:

0.609

AC XY:

45280

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.422

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.457

Gnomad4 EAS

AF:

0.773

Gnomad4 SAS

AF:

0.705

Gnomad4 FIN

AF:

0.728

Gnomad4 NFE

AF:

0.653

Gnomad4 OTH

AF:

0.591

Alfa

AF:

0.632

Hom.:

64286

Bravo

AF:

0.592

TwinsUK

AF:

0.642

AC:

2381

ALSPAC

AF:

0.658

AC:

2536

ESP6500AA

AF:

0.435

AC:

1917

ESP6500EA

AF:

0.638

AC:

5490

ExAC

AF:

0.665

AC:

80727

Asia WGS

AF:

0.699

AC:

2431

AN:

3478

EpiCase

AF:

0.632

EpiControl

AF:

0.638

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 29242559, 28640813, 15732009, 20679634, 19247438, 21173033, 15855350, 21182542) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -

OAS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.87

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.056

MutationTaster

Benign

0.39

P;P;P

GERP RS

2.9

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00080

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over